Viadur

"The U.S. Food and Drug Administration today expanded the approved use of Zytiga (abiraterone acetate) to treat men with late-stage (metastatic) castration-resistant prostate cancer prior to receiving chemotherapy.

WARNINGS

Viadur® (leuprolide acetate implant) , like other LH-RH agonists, causes a transient increase in serum
concentrations of testosterone during the first week of treatment. Patients
may experience worsening of symptoms or onset of new symptoms, including bone
pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction (see
PRECAUTIONS).

Cases of ureteral obstruction and spinal cord compression, which may contribute
to paralysis with or without fatal complications, have been reported with LH-RH
agonists.

If spinal cord compression or renal impairment develops, standard treatment
of these complications should be instituted.

PRECAUTIONS

General

Patients with metastatic vertebral lesions and/or with urinary tract obstruction
should be closely observed during the first few weeks of therapy (see WARNINGS).

X-rays do not affect Viadur® (leuprolide acetate implant) functionality. Viadur® (leuprolide acetate implant) is radio-opaque
and is well visualized on X-rays.

The titanium alloy reservoir of Viadur® (leuprolide acetate implant) is nonferromagnetic and is not
affected by magnetic resonance imaging (MRI). Slight image distortion around
Viadur® (leuprolide acetate implant) may occur during MRI procedures.

Hyperglycemia

Hyperglycemia and an increased risk of developing diabetes have been reported
in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes
mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients
receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia
or diabetes.

Cardiac Disorders

Increased risk of developing myocardial infarction, sudden cardiac death and
stroke has been reported in association with use of GnRH agonists in men. The
risk appears low based on the reported odds ratios, and should be evaluated
carefully along with cardiovascular risk factors when determining a treatment
for patients with prostate cancer. Patients receiving a GnRH agonist should
be monitored for symptoms and signs suggestive of development of cardiovascular
disease and be managed according to current clinical practice.

Information for Patients

Laboratory tests

Response to Viadur® (leuprolide acetate implant) should be monitored by measuring serum concentrations
of testosterone and prostate-specific antigen periodically.

Results of testosterone determinations are dependent on assay methodology.
It is advisable to be aware of the type and precision of the assay methodology
to make appropriate clinical and therapeutic decisions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two-year carcinogenicity studies were conducted in rats and mice. In rats,
dose-related increases of benign pituitary hyperplasia and benign pituitary
adenomas were noted at 24 months when the drug was administered subcutaneously
at high daily doses (4 to 24 mg/m², 50 to 300 times the daily human exposure
based on body surface area). There were significant but not dose-related increases
of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice no
pituitary abnormalities were observed at up to 180 mg/m² (over 2000 times
the daily human exposure based on body surface area) for 2 years.

Mutagenicity studies were performed with leuprolide acetate using bacterial
and mammalian systems. These studies provided no evidence of a mutagenic potential.